Angiogenesis is a key process in tumour growth and metastasis, and Factor-VIII microvascular density has been found to influence prognosis among endometrial carcinoma patients. The CD105/endoglin antibody has been reported to preferentially bind to activated endothelial cells in tissues participating in angiogenesis, and we therefore wanted to compare the prognostic significance of CD105/endoglin to that of Factor-VIII. In a population-based endometrial carcinoma study with long (median 11.5 years) and complete patient follow-up, mean intratumour microvascular density (MVD) assessed using CD105/endoglin was investigated and compared with previous data for MVD assessed using Factor-VIII. MVD by CD105/endoglin was significantly correlated with MVD by Factor-VIII (p=0.001). However, tumours within the two groups defined by the upper and lower quartiles for CD105/endoglin-MVD were both significantly more often metastatic (FIGO-stage III/IV; p=0.03), with high tumour cell proliferation by Ki67 (p=0.007) and with reduced survival (p=0.036) as compared with the intermediate groups. In Cox regression analysis, CD105/endoglin-MVD showed independent prognostic influence when analysed together with patient age, FIGO stage, histologic subtype, histologic grade and Factor-VIII-MVD, while the latter lost its prognostic impact when CD105/endoglin was included. In the subgroup with high MVD, there was a tendency towards improved response to radiation therapy. In conclusion, CD105/endoglin-MVD is significantly associated with FIGO stage, tumour proliferation and prognosis in endometrial carcinoma, indicating that this is a better angiogenic marker in these tumours.
"A significant limitation is the variation in the methods for reporting the topography of the mast cells and macrophages (31). In addition, labeling the vessels for CD31 (24,25,27,28) or CD105 (33,34), the mast cells for tryptase (24,25,35), toluidine blue (27) or C-kit (26) and the macrophages for CD68 (29–31) or CD163 (28) may cause discrepancies. "
[Show abstract][Hide abstract] ABSTRACT: The present study aimed to observe and compare the values of microvessel density (MVD), mast cell microdensity (McMD) and macrophage microdensity (MphMD) in intratumoral areas compared with the advancing edges, and to assess any correlations between these values and the degree and stage of the neoplasia. The cases of 52 patients who were diagnosed with endometrial carcinoma between 2003 and 2011 were analyzed, the majority of which were in the first stage of the disease (44 cases). Double sequential immunohistochemistry and the hot-spot counting method were used to assess the MVD (CD105(+) MVD), McMD [tryptase(+) (Try(+)) McMD] and MphMD (CD68(+) MphMD) densities. The χ(2) test, paired Student's t-test and the Pearson correlation index were used to assess the significance of the results. A weak correlation was observed at the advancing edge only, between CD105(+) MVD and Try(+) McMD (P=0.039). No significant differences were identified in the analysis of CD105(+) MVD, Try(+) McMD and CD68(+) MphMD, but wide variations in their distribution were observed. Depending on the tumor stage, CD105(+) MVD exhibited an intratumoral, indirect correlation with Try(+) McMD for stage IA (P=0.026) and II (P=0.013) tumors. CD105(+) MVD presented an indirect correlation with CD68(+) MphMD in stage IB tumors (P=0.016) and at the advancing edge for well-differentiated tumors (P=0.027). An analysis of the correlation between CD68(+) MphMD and Try(+) McMD indicated that the intratumoral levels of CD68(+) MphMD were directly proportional with the Try(+) McMD values in well-differentiated (P=0.005) and stage II (P=0.012) tumors, while at the front of the invasion, this correlation was indirect (P=0.010) in stage II tumors. In endometrioid endometrial carcinoma (EEC), angiogenesis is at its most active at the advancing edge of the tumor, where mast cells play a pro-angiogenic role.
"Endoglin expression is a better prognostic marker than other traditional vessels markers, such as CD31 and CD34 [29, 32, 36, 38, 41]. In various tumours endoglin overexpression was associated with lower patient survival rates, presence of node metastases and distant metastatic disease [29–34, 37–41]. Endoglin has been examined as a target of antiangiogenic and antitumor therapy [25, 28]. "
[Show abstract][Hide abstract] ABSTRACT: Endoglin (CD105) is an accessory receptor of transforming growth factor B. The highest synthesis, as well as expression, of endoglin has been found in vascular endothelial cells. The involvement of endoglin in angiogenesis and in angiogenesis-dependent processes has been observed.
Endoglin promotes angiogenesis not only by activation of vascular endothelial cell proliferation but also by induction of the antiapoptotic pathway in hypoxic endothelial cells.
The potential application of endoglin as a tumour angiogenesis marker, useful for cancer diagnostics and clinical application, is anticipated. Endoglin expression may be useful as an indicator of disease progression and helpful for estimation of recurrence and metastasis risk.
"It is well known that these markers are not specific for neo-angiogenic vessels and can express on the pre-existing host vessels. Recently, use of anti-CD105 antibody has been widely accepted due to its relative specificity in identifying microvessels in various tumours [48, 49]. The counting method is critical in determining the number of vessels, MCs or Eos. "
[Show abstract][Hide abstract] ABSTRACT: Neo-angiogenesis is an essential process in physiological and pathological conditions. However, it is a complex process. Several studies demonstrated that intra-tumoural microvessel number is a significant predictor of metastasis and clinical outcome in many tumours, including oral malignancies. The immuno-surveillance cells, mast cells and eosinophils are implicated in the biological behaviour of tumours. Nevertheless, their function in tissues is uncertain. Mast cells are involved in homeostatic regulation of blood vessels as well as host defence. In some malignancies, high mast cell density has been found to correlate with favourable prognosis. However, others reported unfavourable associations. Tumour associated tissue eosinophilia is a well-known phenomena. It has been associated with good and poor prognosis. However, the role of eosinophils in tumours remains controversial. Therefore, this study was designed to investigate the prognostic value of microvessel, mast cell and eosinophil densities in the context of clinico-pathological parameters and survival in squamous cell carcinoma of the tongue.
Anti-CD105 and anti-tryptase monoclonal antibodies were utilized to highlight and count microvessels and mast cells respectively in 81 cases of tongue squamous cell carcinoma. Eosinophils were demonstrated using carbol chromotrope histochemical stain. The densities were counted per mm2 and correlated with patients' outcome and other clinico-pathological parameters using non-parametric tests and student's t-test. Clinically, the cases were divided into 4 main groups depending on survival time, lymph-node or distant metastasis.
The 5 year survival was significantly lower in patients with a low mast cell density than those with a high density (p=0.006, Kruskal-Wallis test). The survival group-A demonstrated significantly higher mast cell and microvessel numbers than group-D (p=0.007, student's t-test) respectively. Patients with well- differentiated squamous cell carcinoma had significantly higher numbers of mast cells when compared to patients with poorly differentiated squamous cell carcinoma (p<0.05, student's t-test). The lymph node involvement correlation between the survival group-A and survival group-D was also significant (p=0.001, Mann-Whitney U test).
Data from this study indicates that accumulating mast cells in tumours play a part in inhibiting tumour progression and is potentially angiogenic in tumours.
Libyan Journal of Medicine 03/2007; 2(1):30-9. DOI:10.4176/070110 · 1.06 Impact Factor
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